PROBUCOL INHIBITS MONONUCLEAR CELL-ADHESION TO VASCULAR ENDOTHELIUM IN THE CHOLESTEROL-FED RABBIT

Mononuclear cells, isolated from the blood of hyperlipidaemic patients , are hyper-reactive and possess an increased propensity to adhere to vascular endothelial cells. Hyperlipidaemia is also associated with a dysfunctional endothelium, to which mononuclear cells stick with great er avidity. In order to assess the importance of lipid peroxidation an d free-radical generation in these processes, we have investigated the effects of probucol on mononuclear cell adhesion to vascular endothel ial cells in vivo and in vitro in the cholesterol-fed rabbit. New Zeal and White rabbits were fed either: (i) control chow (n = 15), (ii) 2% cholesterol (n = 11), or (iii) 2% cholesterol with 1 % probucol (n = 1 1). Mononuclear cell adherence to endothelium in the common carotid ar tery was assessed 5 weeks after the start of the experimental diet usi ng the Hoechst 33342 staining technique. The 2% cholesterol diet cause d a more than 6-fold increase in mean mononuclear cell adherence (P < 0.001). Concurrent probucol therapy abrogated the effects of cholester ol feeding, and in animals in this group, in vivo mononuclear cell adh erence did not differ significantly from control animals. In vivo mono nuclear cell adherence was directly related to serum cholesterol level s (r = 0.68, P < 0.0001) and inversely related to serum probucol conce ntrations (r = -0.63, P < 0.002). Concurrent probucol therapy also red uced the in vitro binding of mononuclear cells, isolated from hypercho lesterolaemic animals, to endothelial cell monolayers (P < 0.01). Thes e data suggest that the increased binding of mononuclear cells to vasc ular endothelium of cholesterol-fed rabbits may be a free radical medi ated process that is inhibited by antioxidants.